Antibiotic production is often governed by large gene clusters composed of genes related to antibiotic scaffold synthesis, tailoring, regulation, and resistance. With the expansion of genome sequencing, a considerable number of antibiotic gene clusters has been isolated and characterized. The emerging genome engineering techniques make it possible towards more efficient engineering of antibiotics. In addition to genomic editing, multiple synthetic biology approaches have been developed for the exploration and improvement of antibiotic natural products. Here, we review the progress in the development of these genome editing techniques used to engineer new antibiotics, focusing on three aspects of genome engineering: direct cloning of large genomic fragments, genome engineering of gene clusters, and regulation of gene cluster expression. This review will not only summarize the current uses of genomic engineering techniques for cloning and assembly of antibiotic gene clusters or for altering antibiotic synthetic pathways but will also provide perspectives on the future directions of rebuilding biological systems for the design of novel antibiotics.

中文翻译：

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基因组工程和对合成生物学的修饰以生产抗生素。

抗生素的生产通常受大型基因簇支配，这些簇由与抗生素支架合成，修饰，调节和抗性相关的基因组成。随着基因组测序的扩展，已经分离和表征了许多抗生素基因簇。新兴的基因组工程技术使抗生素的更有效工程成为可能。除了基因组编辑外，还开发了多种合成生物学方法来探索和改善抗生素天然产物。在这里，我们回顾了用于工程改造新抗生素的基因组编辑技术的开发进展，重点关注基因组工程的三个方面：大基因组片段的直接克隆，基因簇的基因组工程和基因簇表达的调控。